Physiological Response of Adipocytes to Weight Loss and Maintenance

Background

Metabolic processes in adipose tissue are dysregulated in obese subjects and, in response to weight loss, either normalize or change in favor of weight regain.

Objective

To determine changes in adipocyte glucose and fatty acid metabolism in relation to changes in adipocyte size during weight loss and maintenance.

Methods

Twenty-eight healthy subjects (12 males), age 20–50 y, and BMI 28–35 kg/m², followed a very low energy diet for 2 months, followed by a 10-month period of weight maintenance. Body weight, body composition (deuterium dilution and BodPod), protein levels (Western blot) and adipocyte size were assessed prior to and after weight loss and after the 10-month follow-up.

Results

A 10% weight loss resulted in a 16% decrease in adipocyte size. A marker for glycolysis decreased (AldoC) during weight loss in association with adipocyte shrinking, and remained decreased during follow-up in association with weight maintenance. A marker for fatty acid transport increased (FABP4) during weight loss and remained increased during follow-up. Markers for mitochondrial beta-oxidation (HADHsc) and lipolysis (ATGL) were only increased after the 10-month follow-up. During weight loss HADHsc and ATGL were coordinately regulated, which became weaker during follow-up due to adipocyte size-related changes in HADHsc expression. AldoC was the major denominator of adipocyte size and body weight, whereas changes in ATGL during weight loss contributed to body weight during follow-up. Upregulation of ATGL and HADHsc occured in the absence of a negative energy balance and was triggered by adipocyte shrinkage or indicated preadipocyte differentiation.

Conclusion

Markers for adipocyte glucose and fatty acid metabolism are changed in response to weight loss in line with normalization from a dysregulated obese status to an improved metabolic status.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01015508","term_id":"NCT01015508"}}NCT01015508     

Blood profile of proteins and steroid hormones predicts weight change after weight loss with interactions of dietary protein level and glycemic index

Background

Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI) diet improved weight maintenance.

Objective

To identify blood predictors for weight change after weight loss following the dietary intervention within the Diogenes study.

Design

Blood samples were collected at baseline and after 8-week low caloric diet-induced weight loss from 48 women who continued to lose weight and 48 women who regained weight during subsequent 6-month dietary intervention period with 4 diets varying in protein and GI levels. Thirty-one proteins and 3 steroid hormones were measured.

Results

Angiotensin I converting enzyme (ACE) was the most important predictor. Its greater reduction during the 8-week weight loss was related to continued weight loss during the subsequent 6 months, identified by both Logistic Regression and Random Forests analyses. The prediction power of ACE was influenced by immunoproteins, particularly fibrinogen. Leptin, luteinizing hormone and some immunoproteins showed interactions with dietary protein level, while interleukin 8 showed interaction with GI level on the prediction of weight maintenance. A predictor panel of 15 variables enabled an optimal classification by Random Forests with an error rate of 24±1%. A logistic regression model with independent variables from 9 blood analytes had a prediction accuracy of 92%.

Conclusions

A selected panel of blood proteins/steroids can predict the weight change after weight loss. ACE may play an important role in weight maintenance. The interactions of blood factors with dietary components are important for personalized dietary advice after weight loss.

Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00390637","term_id":"NCT00390637"}}NCT00390637     

Cerebellar LTD and pattern recognition by Purkinje cells

Many theories of cerebellar function assume that long-term depression (LTD) of parallel fiber (PF) synapses enables Purkinje cells to learn to recognize PF activity patterns. We have studied the LTD-based recognition of PF patterns in a biophysically realistic Purkinje-cell model. With simple-spike firing as observed in vivo, the presentation of a pattern resulted in a burst of spikes followed by a pause. Surprisingly, the best criterion to distinguish learned patterns was the duration of this pause. Moreover, our simulations predicted that learned patterns elicited shorter pauses, thus increasing Purkinje-cell output. We tested this prediction in Purkinje-cell recordings both in vitro and in vivo. In vitro, we found a shortening of pauses when decreasing the number of active PFs or after inducing LTD. In vivo, we observed longer pauses in LTD-deficient mice. Our results suggest a novel form of neural coding in the cerebellar cortex.     

Intermediate stage complex regional pain syndrome type 1 is unrelated to proinflammatory cytokines

The aim of this paper is to determine the involvement of tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 in intermediate CRPS 1 as locally formed mediators of inflammation. In this study, 25 patients with proven CRPS 1 (Bruehl criteria) were included. All patients participated in one of our earlier studies during the acute stage of their disease. After the disease developed into an intermediate stage, both the disease activity and the profile of inflammatory mediators were reevaluated. Disease activity and impairment were determined by means of a visual analogue scale, the McGill Pain Questionnaire, the difference in volume and temperature between the involved and uninvolved extremities, and the reduction in active range of motion of the involved extremity. Suction blisters were made on the involved and uninvolved extremities for measurement of IL-6 and TNF-alpha. A significant improvement in signs and symptoms of impairment was found. However, the levels of IL-6 and TNF-alpha in blister fluid in the involved extremity versus uninvolved extremity were still significantly raised. Although signs and symptoms are significantly improved, proinflammatory cytokines are still increased in CRPS 1 affected extremities during the intermediate stage of the disease. This indicates that the initiation and sustained development of the disease are only partially affected by proinflammatory cytokines. Follow-up in the chronic stage is necessary to draw more definite conclusions about the existence of a supposed relation between clinical signs and symptoms and the level of proinflammatory cytokines.     

Phylogenetics of Stelis and closely related genera (Orchidaceae: Pleurothallidinae)

Stelis, one of the largest genera within Pleurothallidinae, was recently recircumscribed to include a few hundred more species, most of which had previously been assigned to Pleurothallis. Here, a new phylogenetic analysis of Stelis and closely related genera based on DNA sequences from nuclear ITS and chloroplast matK, based on a much larger sample, is presented; it includes more than 100 species assigned to Stelis and covers all proposed groupings within the genus, many of which have not previously been represented. Clades are proposed to enable easier discussion of groups of closely related species; each clade is characterized morphologically, ecologically, and geographically to explain the evidence found in the molecular analysis. Discussion of the evolutionary trends of character states found in the genus in its broad sense is given. The current taxonomy of the group is given and the possible taxonomical implications of the findings presented here are discussed.     

Proteomic analysis of log to stationary growth phase Lactobacillus plantarum cells and a 2-DE database

Lactobacillus plantarum is part of the natural microbiota of many food fermentations as well as the human gastro-intestinal tract. The cytosolic fraction of the proteome of L. plantarum WCFS1, whose genome has been sequenced, was studied. 2-DE was used to investigate the proteins from the cytosolic fraction isolated from mid- and late-log, early- and late-stationary phase cells to generate reference maps of different growth conditions offering more knowledge of the metabolic behavior of this bacterium. From this fraction, a total of 200 protein spots were identified by MALDI-MS and a proteome production map was constructed to facilitate further studies such as detection of suitable biomarkers for specific growth conditions. More than half (57%) of the identified proteins were predicted to be involved in metabolic pathways of the bacterium. The protein profile changed during the growth of the bacteria such that 29% of the identified proteins involved in anabolic pathways were at least twofold up-regulated throughout the mid- and late-exponential and early-stationary phases. In the late-stationary phase, six proteins involved in stress or with a potential role for survival during starvation were up-regulated significantly.